At the end of 2008, state and federal prisons held more than 1.6 million prisoners. Major depressive disorder (MDD) is one of the most common disorders in prison settings, with 12 month prevalence rates that are 3 times those of individuals in the community (23.5%). The high rate of MDD among prisoners is of public health concern because prisoners are particularly vulnerable to the negative consequences of MDD, including suicide, dropout from correctional programming, rejection and victimization by other inmates, and difficulty addressing medical, family, and substance use problems. MDD also increases prison costs and risk of prison and substance use recidivism. Despite the prevalence and serious consequences of MDD among prisoners, the only randomized trial of treatments for MDD in prisons or jails larger than 10 people was conducted by the PI in pilot work for this proposal (see below). RFA- MH-11-061 calls for "studies that target disorders commonly encountered in justice settings for which there are existing mental health interventions with proven effectiveness in other settings... Of particular priority are studies addressing the delivery of mental health treatment during incarceration." This study will examine the effects of an evidence-based, first-line treatment for MDD, interpersonal psychotherapy (IPT), among prisoners, and will be the first fully-powered randomized trial of treatment for MDD in any incarcerated population. IPT's multicultural appeal and ability to be delivered by non-PhD or MSW level interventionists are assets in prisons, where many inmates come from minority groups and many front-line counselors have bachelor's degrees and little or no specialized mental health training. These features and IPT's effectiveness in a group format give it good potential for uptake within the prison system. Our prison pilot work (supported by an NIH K23 award to the PI) indicates that: (a) group IPT for MDD was feasible, acceptable, and effective among female prisoners;(b) prison stakeholders see MDD treatment as extremely important;and (c) non-specialty prison counselors can deliver IPT adherently and competently. This 3-year R01 will compare group IPT to treatment as usual (TAU) in a sample of 90 male and 90 female prisoners with MDD from 4 institutions during treatment and 3-month follow-up. Effectiveness outcomes include: 1. Depressive symptoms. 2. Suicidality. 3. In-prison functioning (i.e., enrollment and completion of correctional programs;disciplinary and incident reports;aggression/victimization;social support). Pilot implementation outcomes include: 4. Cost of group IPT and of TAU for MDD;5. Feasibility and acceptability of IPT to all stakeholders;6. Prison provider intervention fidelity;7. Prison provider attitudes and competencies;8. Stakeholder perspectives on barriers and facilitators to examine in a subsequent implementation study. We anticipate that this study will establish the effectiveness of IPT for MDD in prisons, will assess its cost, and will provide the foundation for research on implementation of evidence-based treatments for a severe and prevalent disorder among this vulnerable, understudied population PUBLIC HEALTH RELEVANCE: Major depressive disorder (MDD) is a severe mental illness that is extremely common in prison settings. The high rate of MDD among prisoners is a concern because they are especially vulnerable to negative consequences of depression, including suicide, inability to protect oneself while incarcerated, dropout from correctional treatment and education programs, prison recidivism, relapse to addiction, and difficulty addressing a wide array of medical and psychosocial stressors such as HIV, trauma, poverty, and homelessness. This study will test an evidence-based treatment for MDD in men's and women's prisons, and will be the first large-scale randomized trial of treatments for MDD in any incarcerated population.